Virus hemagglutinins, sialic acid interaction

Examples of glyco-coated dendrimers are the sialylated dendrimers79 that have been developed to prevent infection by the influenza virus. This infection is mediated by the interaction of viral glycoprotein hemagglutinin and the sialic acid residues present on cell-surface glycoproteins and glycolipids. 

Figure 11.29 Viral receptors. Influenza virus targets cells by binding to sialic acid residues (purple diamonds) located at the termini of oligosaccharides present on cell-surface glycoproteins and glycolipids. These carbohydrates are bound by hemagglutinin (interaction circles), one of the major proteins expressed on the surface of the virus. The other major viral surface protein, neuraminidase, iis an enzyme that cleaves oligosaccharide chains to release the viral particle at a later stage of the viral life cycle.

Influenza neuraminidase cleaves terminal sialic acid residues and destroys the receptors recognized by viral hemagglutinin, which are present on the cell surface, in progeny virions, and in respiratory secretions. This enzymatic action is essential for release of virus from infected cells. Interaction of oseltamivir carboxylate with the neuraminidase causes a conformational change within the enzyme s active site and inhibits its activity. Inhibition of neuraminidase activity leads to viral aggregation at the cell surface and reduced virus spread within the respiratory tract. 

Influenza A viruses are important human and animal pathogens. Their primary natural hosts are aquatic birds from which they are occasionally transmitted to other species. In man they cause outbreaks of respiratory disease that occur as annual epidemics and less frequent pandemics. Influenza B viruses are also believed to be descendants of avian influenza A viruses, but are now largely restricted to humans where they cause respiratory infections as well. Influenza A and B viruses have two envelope glycoproteins, the hemagglutinin (HA) and the neuraminidase (NA), both of which interact with sialic acid. 

Influenza virus A is the primary causative agent responsible for serious cases of human influenza. The influenza infection is initiated by attachment of the virus to the mammalian cell membrane through a process known as hemagglutination. The hemagglutination process is a multivalent interaction between trimers of hemagglutinin (a carbohydrate binding protein present on the viral surface) with multiple sialic acid groups present on the surface of the mammalian epithelial cell. These sialic acid residues are parts of... 

---